Esc2 promotes telomere stability in response to DNA replication stress.

Telomeric regions of the genome are inherently difficult-to-replicate due to their propensity to generate DNA secondary structures and form nucleoprotein complexes that can impede DNA replication fork progression. Precisely how cells respond to DNA replication stalling within a telomere remains poorly characterized, largely due to the methodological difficulties in analysing ...
defined stalling events in molecular detail. Here, we utilized a site-specific DNA replication barrier mediated by the 'Tus/Ter' system to define the consequences of DNA replication perturbation within a single telomeric locus. Through molecular genetic analysis of this defined fork-stalling event, coupled with the use of a genome-wide genetic screen, we identified an important role for the SUMO-like domain protein, Esc2, in limiting genome rearrangements at a telomere. Moreover, we showed that these rearrangements are driven by the combined action of the Mph1 helicase and the homologous recombination machinery. Our findings demonstrate that chromosomal context influences cellular responses to a stalled replication fork and reveal protective factors that are required at telomeric loci to limit DNA replication stress-induced chromosomal instability.
Mesh Terms:
Cell Cycle Proteins, DEAD-box RNA Helicases, DNA Replication, DNA-Binding Proteins, Escherichia coli, Homologous Recombination, Nuclear Proteins, Nucleic Acid Conformation, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Telomere
Nucleic Acids Res.
Date: Dec. 21, 2018
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